Polyurethane (PU) elastomers have excellent mechanical properties and high blood and tissue compatibility. They are widely used in biological implants ranging from catheters to artificial heart valves Their use in long-term implantation is unsatisfactory due to biologically induced hydrolysis and enzymatic and oxidative degradation. Attention has focused on the flexible soft segments and the right hard domains as prime factors in determining a PU's biostability. Ether-based soft segments undergo slow oxidation and subsequent chain cleavage, while some aliphatic soft segments undergo slow oxidation and subsequent chain cleavage, while some aliphatic soft segments become oxidatively crosslinked and brittle. The polymer's hard domains inhibit degradation by shielding the urethane linkages from hydrolysis. Numerous studies have investigated PU biostability, unfortunately both their typically narrow scope and their minimal ability to control hard domain morphology have made it virtually impossible to uncover the complex interrelationships between hard domains, soft segments, and biostability. The objective of this study is to develop polyurethane elastomers with maximal biostability. Three aspects of this study will contribute dramatically to its success. First is the invention by the PI of technology to control the phase separation (and thereby physical properties) of PU elastomers independent to the hydrophobicity of the polyurethane soft segment. Second, the new technology allows the use of statistically designed experimental protocols to model the effect each chemical and morphological change has on polymer biostability. The experiments will also determine the interactions between these variables. The models will enable finer control of hard domain formation and, thereby, polymer physical properties and biostability. Also a very wide range of PU precursors will be used to guarantee that all polymer subtypes are tested. Finally, a solid-state NMR, DMA, and IR spectroscopy (among others) will enable testing of hypotheses concerning the role each chemical change has on the polymer morphology and biostability The Specific Aims are: 1. Use model compounds to confirm the sites which are susceptible to biological attack and identify the degradation products. 2. Investigate how the new technology modifies phase separation within PU polymers, and determine phase characteristics of maximally biostable polymers. 3. Use statistically designed experiments to investigate the interplay between the polymers' chemical functionality, hydrophobicity, morphology, crosslink density on polymer stability in vitro. 4. Develop maximally biostable polyurethane elastomers; measure success using in vitro degradation protocols. 5. Bring the most promising elastomers through small animal in vivo stability studies to test and refine the hypotheses.